pseudomycin-b and Cryptococcosis

With the aim of identifying safer pseudomycin derivatives, we synthesized and evaluated a number of N-acyloxymethyl carbamate linked prodrugs of 3-amido pseudomycin analogues. To our satisfaction, all of the prodrug-amide combinations prepared exhibited good in vivo efficacy against murine Candidiasis. When evaluated in a dose elevation study, all of the newly synthesized combinations (e.g., 4A, 6A, 8A, and 8B) demonstrated improved toxicity profiles in comparison to their corresponding 3-amides as well as the parent pseudomycin B.

Topics: Amides; Animals; Antifungal Agents; Aspergillus fumigatus; Candida albicans; Candidiasis; Carbamates; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Mice; Microbial Sensitivity Tests; Peptides, Cyclic; Prodrugs